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la velocidad de sedimentaci&#243;n globular &#40;VSG&#41; y el tabaquismo&#46; Los estudios m&#225;s recientes tambi&#233;n involucran a los anticuerpos antip&#233;ptidos citrulinados &#40;ACPA&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a>&#46; Debido a la conexi&#243;n entre el humo del tabaco y el desarrollo de ACPA&#44; se cree que este t&#243;xico puede influir tanto en la patog&#233;nesis de la AR como en sus complicaciones<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a>&#46; Por lo tanto&#44; fumar podr&#237;a ser un factor de riesgo prevenible para la susceptibilidad a la AR&#44; a la EPID asociada a AR y a la fibrosis pulmonar idiop&#225;tica<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El tratamiento fundamental de la AR son los f&#225;rmacos modificadores de la enfermedad &#40;FAME&#41; sint&#233;ticos &#40;FAMEs&#41; y biol&#243;gicos &#40;FAMEb&#41;&#44; aunque tambi&#233;n se usan los glucocorticoides&#44; los antiinflamatorios no esteroideos &#40;AINE&#41; y los analg&#233;sicos como tratamiento sintom&#225;tico<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a>&#46; Los estudios en pacientes con AR y EPID tratados con FAME son escasos y contradictorios&#46; Adem&#225;s&#44; estos pacientes normalmente son excluidos de los ensayos cl&#237;nicos debido a esta afectaci&#243;n&#46; Todo esto ha llevado a una restricci&#243;n de su uso y sigue siendo un desaf&#237;o para los cl&#237;nicos&#46; Por lo tanto&#44; se necesita conocer mejor las caracter&#237;sticas de los pacientes tratados con FAME en la pr&#225;ctica cl&#237;nica habitual<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">12&#44;13</span></a>&#46; Los objetivos del presente estudio son&#58; 1&#41;<span class="elsevierStyleHsp" style=""></span>Describir las caracter&#237;sticas cl&#237;nicas&#44; radiol&#243;gicas&#44; pruebas funcionales respiratorias y ecocardiogr&#225;ficas de una cohorte prospectiva de pacientes con AR y EPID cl&#237;nica en tratamiento con FAME en la pr&#225;ctica cl&#237;nica habitual&#44; y 2&#41;<span class="elsevierStyleHsp" style=""></span>estudiar la posible asociaci&#243;n de factores de gravedad &#40;p&#46;ej&#46;&#44; positividad de ACPA&#44; erosiones&#41; con la enfermedad pulmonar asociada a AR&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o del estudio</span><p id="par0020" class="elsevierStylePara elsevierViewall">Estudio transversal multic&#233;ntrico realizado en una cohorte de pacientes con AR y EPID de diferentes hospitales de Andaluc&#237;a&#44; Espa&#241;a&#44; y un grupo control de sujetos con AR sin EPID&#44; pareados por sexo y edad&#46; El per&#237;odo de reclutamiento fue de enero de 2015 a enero de 2017&#46; El estudio fue aprobado por el comit&#233; de &#233;tica m&#233;dica&#44; y todos los sujetos proporcionaron un consentimiento informado por escrito antes de inscribirse&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sujetos</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pacientes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Se reclut&#243; de forma consecutiva a todos los pacientes con AR y EPID tratados con FAME de las consultas de reumatolog&#237;a de diferentes centros de Andaluc&#237;a&#58; Hospital Regional Universitario de M&#225;laga&#44; Hospital Virgen de la Victoria de M&#225;laga&#44; Hospital de Valme de Sevilla y Hospital Virgen de las Nieves de Granada&#46; Los criterios de inclusi&#243;n fueron los siguientes&#58; edad &#8805;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; diagn&#243;stico de AR seg&#250;n los criterios de clasificaci&#243;n de la <span class="elsevierStyleItalic">American College of Rheumatology</span>&#47;<span class="elsevierStyleItalic">European League Against Rheumatism 2010</span> &#40;criterios ACR&#47;EULAR 2010&#41;&#44; ILD <span class="elsevierStyleItalic">&#40;American Thoracic Society&#47;European Respiratory Criteria&#41;</span> y tratados en la &#250;ltima visita con FAME&#46; Los criterios de exclusi&#243;n fueron la presencia de cualquier enfermedad inflamatoria o reum&#225;tica distinta a la AR &#40;excepto el s&#237;ndrome de Sj&#246;gren secundario&#41; y embarazo&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Controles</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se seleccionaron consecutivamente pacientes con AR sin EPID de una cohorte prospectiva del Hospital Regional Universitario de M&#225;laga&#46; Los controles fueron pareados por sexo&#44; edad y tiempo de evoluci&#243;n de la enfermedad&#46; Los criterios de inclusi&#243;n fueron&#58; edad &#8805;<span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>a&#241;os&#44; diagn&#243;stico de AR seg&#250;n los criterios de clasificaci&#243;n del <span class="elsevierStyleItalic">American College of Rheumatology&#47;European League Against Rheumatism 2010</span> &#40;criterios ACR&#47;EULAR 2010&#41; y tratados en la &#250;ltima visita con FAME&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Protocolo</span><p id="par0035" class="elsevierStylePara elsevierViewall">Los pacientes con AR y EPID que acudieron a consultas de reumatolog&#237;a desde enero de 2015 a diciembre de 2017 y reun&#237;an criterios de selecci&#243;n fueron atendidos seg&#250;n un protocolo preestablecido para recogida de datos&#46; La fecha de esta visita fue usada como fecha &#237;ndice&#44; y esta visita se marc&#243; como V0&#46; Se solicitaron tomograf&#237;a axial computarizada de alta resoluci&#243;n &#40;TACAR&#41;&#44; pruebas funcionales respiratorias &#40;PFR&#41; y ecocardiograma a todos los pacientes que no lo tuvieran en el &#250;ltimo a&#241;o&#46; Los controles fueron atendidos tambi&#233;n con un protocolo preestablecido de recogida de datos</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Variables y definiciones operativas</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Variable principal</span><p id="par0040" class="elsevierStylePara elsevierViewall">Las principales variables analizadas fueron&#58; 1&#41;<span class="elsevierStyleHsp" style=""></span>descripci&#243;n del tipo radiol&#243;gico de EPID en los pacientes con AR&#44; y 2&#41;<span class="elsevierStyleHsp" style=""></span>diferencia en marcadores de gravedad y actividad de la enfermedad en casos y controles en la fecha de inclusi&#243;n&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Otras variables</span><p id="par0045" class="elsevierStylePara elsevierViewall">Las variables de EPID incluyeron la descripci&#243;n del tipo radiol&#243;gico por TACAR &#40;neumon&#237;a intersticial no espec&#237;fica &#91;NINE&#93;&#47;neumon&#237;a intersticial usual &#91;NIU&#93;&#41; y la funci&#243;n pulmonar mediante PFR &#40;DLCO&#44; FEV1&#44; FV&#44; FEV1&#47;CVF&#41;&#59; presencia de hipertensi&#243;n pulmonar &#40;HTP&#41; por ecocardiograma&#44; y presencia y grado de disnea&#46; La TACAR se realiz&#243; en la evaluaci&#243;n basal con una secci&#243;n axial de 1&#44;5 o 2<span class="elsevierStyleHsp" style=""></span>mm de espesor tomada a intervalos de 1<span class="elsevierStyleHsp" style=""></span>cm a lo largo del t&#243;rax y se reconstruy&#243; utilizando un algoritmo de frecuencia espacial alta&#44; adquiri&#233;ndose entre 20-25 cortes para cada paciente&#46; Las exploraciones radiol&#243;gicas por TACAR fueron evaluadas por dos expertos en radiolog&#237;a de t&#243;rax cegados a los datos cl&#237;nicos&#46; Se calific&#243; de acuerdo con la puntuaci&#243;n de Kazerooni en su componente fibr&#243;tico y en la extensi&#243;n de las opacidades del vidrio esmerilado<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; Los patrones de EPID se clasificaron seg&#250;n los criterios de la <span class="elsevierStyleItalic">American Thoracic Society&#47;European Respiratory Criteria</span>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Las variables de AR incluyeron la duraci&#243;n de los s&#237;ntomas&#44; manifestaciones extraarticulares e historia de tabaco&#58; actual o pasada&#46; Adem&#225;s&#44; se recogieron en la fecha de inclusi&#243;n los siguientes par&#225;metros&#58; recuento de articulaciones dolorosas e inflamadas&#44; escala anal&#243;gica visual de 0-10<span class="elsevierStyleHsp" style=""></span>cm&#59; actividad de la enfermedad medido por DAS28 <span class="elsevierStyleItalic">&#40;Disease Activity Score&#41;</span><a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> y funci&#243;n f&#237;sica por un cuestionario de evaluaci&#243;n de salud &#40;HAQ&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a>&#46; Tambi&#233;n se recogieron en la fecha de inclusi&#243;n variables de gravedad&#58; el FR&#44; medido en U&#47;ml&#44; se consider&#243; elevado cuando los t&#237;tulos estaban por encima del punto de corte superior utilizado en nuestro laboratorio &#40;&#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#41; y t&#237;tulo alto &#40;&#62;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#41;&#59; presencia de ACPA&#44; medidos en U&#47;ml&#58; se consideraron positivos con t&#237;tulos superiores a 10<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#44; y t&#237;tulo alto &#40;&#62;<span class="elsevierStyleHsp" style=""></span>340<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#41;&#59; as&#237; como la presencia de erosi&#243;n radiol&#243;gica&#46; Tratamientos&#58; FAMEs&#44; FAMEb&#44; otros inmunosupresores o glucocorticoides con los que est&#225; el paciente en la fecha de inclusi&#243;n&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">An&#225;lisis estad&#237;stico</span><p id="par0055" class="elsevierStylePara elsevierViewall">En primer lugar se realiz&#243; un an&#225;lisis descriptivo de las caracter&#237;sticas en ambos grupos de pacientes&#46; Las variables cualitativas se expresaron como n&#250;mero absoluto y su porcentaje&#59; las variables cuantitativas&#44; como media y desviaci&#243;n t&#237;pica cuando su distribuci&#243;n era normal&#44; y como mediana y rango intercuart&#237;lico si no segu&#237;a la distribuci&#243;n normal&#46; El ajuste de la normalidad de las variables continuas se confirm&#243; con la prueba de Kolgomorov-Smirnov&#46; Se realiz&#243; &#967;<span class="elsevierStyleSup">2</span> o test de Fisher seg&#250;n correspondiera&#44; y para variables cuantitativas&#44; test t de Student para muestras independientes o Mann-Whitney en los casos de no normalidad&#46; Finalmente se realiz&#243; un an&#225;lisis de regresi&#243;n log&#237;stica binaria en pacientes con AR y EPID &#40;VD&#58; EPID&#41; para ver las variables que se asociaban de forma independiente a la presencia de EPID&#46; El tama&#241;o muestral se calcul&#243; asumiendo un riesgo alfa de 0&#44;10 y un riesgo beta de 0&#44;2 en un contraste bilateral&#44; y se precisaron 40 sujetos en cada grupo para detectar como estad&#237;sticamente significativa la diferencia entre dos proporciones&#44; que para el grupo<span class="elsevierStyleHsp" style=""></span>1 se esperaba del 0&#44;53 y para el grupo<span class="elsevierStyleHsp" style=""></span>2 de 0&#44;26<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a>&#46; El an&#225;lisis se llev&#243; a cabo mediante el programa estad&#237;stico Rcomander&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Resultados</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Caracter&#237;sticas basales</span><p id="par0060" class="elsevierStylePara elsevierViewall">La poblaci&#243;n de estudio estuvo compuesta por 82 pacientes con AR&#58; 41 pacientes con AR y EPID y 41 pacientes con AR sin EPID&#46; Todos los pacientes con EPID hab&#237;an sido diagnosticados previamente por TACAR&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se muestran las caracter&#237;sticas basales de ambos grupos de pacientes&#46; Aunque no hubo diferencias entre ambos en la mayor&#237;a de los par&#225;metros cl&#237;nicos y epidemiol&#243;gicos&#44; un mayor porcentaje de pacientes con EPID eran exfumadores &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;013&#41;&#44; con enfermedad erosiva &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;004&#41; y doble o simple seropositividad&#46; Los pacientes con EPID presentaron mayor porcentaje de pacientes con FR positivo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;077&#41;&#44; ACPA positivo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41;&#44; FR y ACPA positivo a t&#237;tulo elevado &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;040&#41;&#46; Los pacientes con AR y EPID tambi&#233;n presentaron una mayor frecuencia de serositis &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;033&#41; y osteoporosis &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Tratamientos&#44; actividad de la enfermedad y funci&#243;n f&#237;sica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Todos los pacientes se encontraban en tratamiento con FAME&#46; Entre los pacientes con AR y EPID&#58; 9 &#40;21&#44;9&#37;&#41; recib&#237;a un FAMEb con un FAMEs&#44; siendo la combinaci&#243;n m&#225;s com&#250;n FAMEs &#43;<span class="elsevierStyleHsp" style=""></span>RTX &#40;12&#44;1&#37;&#41;&#59; 25 pacientes &#40;60&#44;9&#37;&#41; recib&#237;an monoterapia de FAMEs&#44; siendo el metotrexato &#40;MTX&#41; el m&#225;s frecuente &#40;48&#37;&#41;&#44; y 7 &#40;17&#44;0&#41; monoterapia con FAMEb &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; Entre los pacientes con AR sin EPID la monoterapia con FAMEs es tambi&#233;n la m&#225;s frecuente en 26 pacientes &#40;63&#44;4&#37;&#41;&#44; siendo tambi&#233;n MTX el m&#225;s frecuente&#44; seguido de la terapia combinada en 13 pacientes &#40;31&#44;7&#37;&#41;&#59; solo 2 pacientes se encontraban en monoterapia con un FAMEb &#40;4&#44;8&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">En cuanto a los par&#225;metros de actividad de la enfermedad&#44; no se observaron diferencias en la mediana &#40;p75-p25&#41; en ambos grupos de pacientes en NAD &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;590&#41;&#44; NAI &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;834&#41;&#44; PCR &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;338&#41;&#44; VSG &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;320&#41; ni DAS28 &#40;2&#44;7 &#91;2&#44;3-3&#44;3&#93; vs 2&#44;29 &#91;1&#44;9-3&#44;2&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;145&#41;&#46; S&#237; se mostr&#243; peor calidad de vida en los pacientes con EPID medida por HAQ &#40;1&#44;20 &#91;0&#44;5-1&#44;7&#93; vs 0&#44;75 &#91;0&#44;0-0&#44;0&#93;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Caracter&#237;sticas pulmonares de los pacientes con artritis reumatoide y enfermedad pulmonar intersticial</span><p id="par0075" class="elsevierStylePara elsevierViewall">En cuanto a la cl&#237;nica respiratoria de los pacientes&#44; en la fecha de evaluaci&#243;n la mayor&#237;a describ&#237;an disnea con moderados esfuerzos &#40;25&#59; 61&#44;0&#37;&#41;&#44; 14 pacientes &#40;34&#44;1&#37;&#41; no presentaban disnea y solo 2 pacientes &#40;4&#44;9&#37;&#41; presentaban disnea de m&#237;nimos esfuerzos con oxigenoterapia domiciliaria&#46; Los pacientes sin disnea presentaban mayor media &#40;DE&#41; de satO<span class="elsevierStyleInf">2</span> que los pacientes con disnea de moderado y m&#237;nimo esfuerzo &#40;97&#44;15 &#91;2&#44;5&#93; vs 95&#44;12 &#91;2&#44;2&#93; vs 95&#44;0 &#91;0&#44;7&#93;&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Entre las alteraciones en las PFR se observ&#243; disminuci&#243;n de la capacidad de difusi&#243;n de DLCO en la mayor&#237;a de los pacientes&#46; La capacidad vital forzada &#40;CVF&#41; y el volumen espiratorio forzado en un segundo &#40;FEV1&#41; estaban por debajo de 80 en algo m&#225;s de la mitad de los pacientes&#44; pero la relaci&#243;n FEV1&#47;CVF fue mayoritariamente normal &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46; La DLCO &#60;<span class="elsevierStyleHsp" style=""></span>70 se asoci&#243; con erosiones &#40;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; FR elevado &#40;0&#44;038&#41; y ACPA positivo &#40;0&#44;039&#41;&#46; Cuatro pacientes &#40;9&#44;8&#37;&#41; presentaban HTP por ecocardiograma&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Los tipos histopatol&#243;gicos descritos por TACAR m&#225;s comunes fueron la neumon&#237;a intersticial usual en 27 pacientes &#40;65&#44;9&#37;&#41; y la neumon&#237;a intersticial inespec&#237;fica en 13 &#40;31&#44;7&#37;&#41;&#46; Solo un paciente &#40;2&#44;3&#37;&#41; presentaba una neumon&#237;a de tipo organizada&#46; En 3 pacientes hubo una combinaci&#243;n de tipos histopatol&#243;gicos NINE y NIU&#44; pero finalmente se describi&#243; en el tipo dominante&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Factores asociados a enfermedad pulmonar intersticial en artritis reumatoide</span><p id="par0090" class="elsevierStylePara elsevierViewall">En el an&#225;lisis multivariante se observ&#243; que los pacientes con historia de tabaco de al menos 6<span class="elsevierStyleHsp" style=""></span>meses y con artritis erosiva triplicaban el riesgo de EPID&#46; As&#237; mismo&#44; la variable que m&#225;s se asoci&#243; a la EPID de forma independiente fue la presencia de ACPA &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#44;91&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46; Este modelo explicar&#237;a el 36&#37; de la variabilidad de la presencia de EPID &#40;R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;36&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discusi&#243;n</span><p id="par0095" class="elsevierStylePara elsevierViewall">Los pacientes con AR en tratamiento con FAME y EPID de nuestra cohorte presentan predominante un patr&#243;n histopatol&#243;gico por TACAR tipo NIU &#40;65&#44;9&#37;&#41; o NINE &#40;31&#44;7&#37;&#41;&#44; porcentajes similares a los descritos en la literatura<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">14&#44;15</span></a>&#46; Tambi&#233;n hay que se&#241;alar que casi el 90&#37; de nuestros pacientes presentaban una disminuci&#243;n de la DLCO&#46; Estas cifras coinciden con otros estudios&#44; como el de Zhang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a>&#44; que encuentran disminuci&#243;n de DLCO en el 92&#37; de pacientes con AR y EPID y la describen como el cambio fisiopatol&#243;gico m&#225;s com&#250;n y sensible de la EPID&#46; Esto tiene inter&#233;s diagn&#243;stico y tambi&#233;n podr&#237;a tenerlo de cribado desde el inicio de la enfermedad&#46; De hecho&#44; un estudio reciente realizado en pacientes con AR se&#241;ala la DLCO como un buen m&#233;todo para identificar desde forma precl&#237;nica a los pacientes con EPID y AR<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a>&#46; En este &#250;ltimo estudio tambi&#233;n se describe una correlaci&#243;n inversa entre los niveles de DLCO y t&#237;tulo de ACPA &#40;&#8722;0&#44;45&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;004&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a>&#46; En nuestra cohorte los pacientes con EPID con DLCO<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80 se asoci&#243; con erosiones &#40;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; FR elevado &#40;0&#44;038&#41; y ACPA positivo &#40;0&#44;039&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Los pacientes con AR y EPID de nuestra cohorte presentan una enfermedad m&#225;s grave en forma de mayor asociaci&#243;n a enfermedad erosiva y a presencia de ACPA&#46; Tambi&#233;n identificamos un mayor n&#250;mero de pacientes con historia de h&#225;bito tab&#225;quico en pacientes con EPID&#46; La mayor prevalencia de ACPA detectada en pacientes con AR-EPID respecto a AR sin EPID objetivada en nuestros pacientes es acorde a la mayor&#237;a de los estudios<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5&#44;18-20</span></a>&#44; aunque existen algunos en los cuales no se objetiv&#243; esta asociaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">21&#44;22</span></a>&#46; Estas diferencias podr&#237;an ser explicadas por el tipo de poblaci&#243;n&#44; por la definici&#243;n de la enfermedad o por la metodolog&#237;a para detectar los par&#225;metros cl&#237;nicos&#46; La sensibilidad y la especificidad variables de los m&#233;todos para la detecci&#243;n de ACPA tambi&#233;n pueden afectar su valor al evaluar la asociaci&#243;n con EPID&#46; La positividad significativamente m&#225;s alta en los pacientes con AR y EPID puede indicar que la presencia de ACPA puede ser un buen biomarcador para el diagn&#243;stico de EPID en pacientes con AR&#46; Se cree que la lesi&#243;n pulmonar por el tabaquismo y otros est&#237;mulos puede contribuir a la modificaci&#243;n de citrulinaci&#243;n de las prote&#237;nas&#44; que luego crea nuevos ep&#237;topos y respuestas autoinmunes posteriores<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a>&#59; en este sentido&#44; en nuestro estudio se ha observado que una historia previa de tabaco &#40;durante al menos 6<span class="elsevierStyleHsp" style=""></span>meses&#41; est&#225; asociada a la EPID en AR&#44; y m&#250;ltiples estudios han demostrado esta asociaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">23&#44;24</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En cuanto al tratamiento utilizado&#44; los pacientes con AR y EPID tomaban m&#225;s FAMEs que los pacientes sin EPID&#44; fundamentalmente a expensas de MTX&#59; esto podr&#237;a ser por los datos contradictorios descritos con este&#58; un metaan&#225;lisis de ensayos controlados aleatorizados donde describen un aumento del riesgo de neumonitis asociado con MTX &#40;RR&#58;<span class="elsevierStyleHsp" style=""></span>7&#44;81&#44; IC<span class="elsevierStyleHsp" style=""></span>95&#37;&#58; 1&#44;76-34&#44;72&#41;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a>&#46; Posteriormente un grupo de expertos expusieron su desacuerdo con lo anterior&#44; entre otras cosas por la definici&#243;n inespec&#237;fica del t&#233;rmino neumonitis<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a>&#46; Estos describieron la evoluci&#243;n de la funci&#243;n pulmonar en una cohorte de pacientes con AR y EPID y observaron una mejora en PFR tras tratamiento con corticoides m&#225;s FAME &#40;MTX&#44; LFN o AZA&#41;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a>&#46; En cuanto al tratamiento biol&#243;gico empleado en nuestra cohorte&#44; fue el mismo en ambos grupos de pacientes&#46; Con respecto al tratamiento con FAMEb&#44; en estos pacientes la evidencia es a&#250;n m&#225;s incierta&#46; Los pocos estudios llevados a cabo describen a abatacept y rituximab como f&#225;rmacos que podr&#237;an ser eficaces y seguros en el tratamiento de AR con EPID&#44; tanto a nivel articular como en la estabilizaci&#243;n&#44; incluso con mejor&#237;a en par&#225;metros respiratorios<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">28&#44;29</span></a>&#46; Coincidiendo con estos datos descritos&#44; la distribuci&#243;n del uso de terapia biol&#243;gica en nuestros pacientes fue concordante&#58; mayor uso de rituximab y abatacept en pacientes con EPID frente a anti-TNF y tocilizumab en el grupo sin EPID&#46; El hecho de que ambos grupos de pacientes est&#233;n en tratamiento podr&#237;a ser la causa de que no haya diferencias en la actividad inflamatoria medida por DAS28 y RFA &#40;PCR y VSG&#41; en ambos grupos de pacientes&#46; El estudio de Restrepo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a>&#44; al igual que el nuestro&#44; tambi&#233;n presenta un menor porcentaje de pacientes con EPID tratados con MTX por datos contradictorios en cuanto a su toxicidad pulmonar&#59; sin embargo&#44; ellos asocian dicho infratratamiento con un mayor DAS28 en estos pacientes&#46; Quiz&#225;s esto pueda ser debido a que los pacientes con EPID de su estudio ten&#237;an una mayor edad y una mayor duraci&#243;n de la enfermedad que aquellos sin EPID&#44; algo que no ocurre en nuestro estudio&#44; por parearlos por sexo&#44; edad y tiempo de evoluci&#243;n&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Entre las limitaciones de este estudio&#44; al tratarse de un estudio realizado en pr&#225;ctica cl&#237;nica habitual&#44; no se ha realizado PFR ni TACAR en el grupo de pacientes con AR sin diagn&#243;stico de EPID por no tener ninguna cl&#237;nica asociada y tener radiograf&#237;as de t&#243;rax sin alteraciones&#46; Aunque seg&#250;n diversos trabajos<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a> ya desde fase precl&#237;nica podr&#237;a haber alteraciones en PFR y TACAR&#44; en estos pacientes de pr&#225;ctica cl&#237;nica se solicitaron estas pruebas en presencia de sospecha de afectaci&#243;n pulmonar&#46; Este estudio se trata de un an&#225;lisis observacional de una cohorte de pacientes con AR y EPID&#44; en los que estamos analizando prospectivamente los par&#225;metros de funci&#243;n respiratoria a lo largo del tiempo&#44; y una cohorte de pacientes con AR sin cl&#237;nica respiratoria&#46; El estudio se ha realizado en condiciones de pr&#225;ctica cl&#237;nica habitual y sus resultados podr&#237;an extrapolarse a situaciones en este &#225;mbito&#44; aunque para confirmar los hallazgos encontrados en nuestro estudio y establecer causalidad ser&#237;an necesarios estudios longitudinales con un mayor n&#250;mero de pacientes&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; los resultados de nuestro estudio apoyan la mayor frecuencia del patr&#243;n histopatol&#243;gico NIU y NINE en pacientes con AR y EPID&#44; as&#237; como la alteraci&#243;n de la DLCO como par&#225;metro m&#225;s importante&#46; Los pacientes con AR y EPID se asocian a una enfermedad m&#225;s grave &#40;erosiones y presencia de ACPA&#41; as&#237; como al factor de exposici&#243;n al tabaco&#46; El tratamiento con FAME en ambos grupos de pacientes permite el control de la actividad inflamatoria&#44; con un mayor uso de HQC y leflunomida entre los sint&#233;ticos&#44; y rituximab y abatacept entre los biol&#243;gicos&#44; en pacientes con EPID&#46; Ser&#225; necesario esperar la evaluaci&#243;n prospectiva de estos pacientes para ver la posible asociaci&#243;n del tratamiento con la evoluci&#243;n de la enfermedad pulmonar&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Financiaci&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">Fundaci&#243;n P&#250;blica Andaluza para la Investigaci&#243;n de M&#225;laga en Biomedicina y Salud &#40;FIMABIS&#41;&#46; Fundaci&#243;n Espa&#241;ola de Reumatolog&#237;a &#40;FER&#41;&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicto de intereses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Natalia Mena-V&#225;zquez&#58; charlas para MSD&#44; UCB y Roche&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Lorena P&#233;rez-Albaladejo&#58; no tiene conflicto de intereses&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Sara Manrique-Arija&#58; charlas&#47;ponencias para Abbvie&#44; Pzifer y MSD&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Carmen Mar&#237;a Romero-Barco&#58; charlas&#47;ponencias para Abbvie&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Carmen G&#243;mez Cano&#58; no tiene conflicto de intereses&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Inmaculada Ure&#241;a-Garnica&#58; no tiene conflicto de intereses&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Antonio Fern&#225;ndez-Nebro&#58; charlas&#47;ponencias para Roche&#44; MSD y BMS&#46;</p></span></span>"
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              "titulo" => "Caracter&#237;sticas pulmonares de los pacientes con artritis reumatoide y enfermedad pulmonar intersticial"
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              "identificador" => "sec0080"
              "titulo" => "Factores asociados a enfermedad pulmonar intersticial en artritis reumatoide"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Estudiar las diferencias en pacientes con artritis reumatoide &#40;AR&#41; y enfermedad pulmonar intersticial &#40;EPID&#41; y pacientes con AR sin EPID&#44; e identificar factores asociados con la EPID en pacientes con AR&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional de casos y controles&#46; Pacientes&#58; se seleccionaron pacientes de una cohorte con AR y EPID de diferentes centros de Andaluc&#237;a&#46; Controles&#58; pacientes con AR sin EPID pareados por edad&#44; g&#233;nero y tiempo de evoluci&#243;n&#46; Protocolo&#58; los pacientes con AR se revisan cada 3-6<span class="elsevierStyleHsp" style=""></span>meses en consulta&#46; Todos los pacientes son revisados de acuerdo con un protocolo predeterminado con recogida de datos sistem&#225;tica&#46; Desenlaces&#58; descripci&#243;n del tipo radiol&#243;gico de EPID&#44; diferencias en los marcadores de gravedad en casos y controles y en la actividad de la enfermedad&#46; Otras variables&#58; descripci&#243;n del tipo de EPID por TACAR&#58; neumon&#237;a intersticial usual &#40;NIU&#41;&#44; neumon&#237;a intersticial no espec&#237;fica &#40;NINE&#41; y de la funci&#243;n pulmonar por PFR&#59; marcadores de actividad y gravedad de artritis&#58; DAS28&#44; HAQ&#44; FR&#44; ACPA&#44; erosiones&#46; Tratamiento con FAME&#46; An&#225;lisis&#58; descriptivo&#44; &#967;<span class="elsevierStyleSup">2</span> o t de Student&#44; seguida de regresi&#243;n log&#237;stica binaria &#40;Vd&#58;EPID en pacientes con AR&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 82 pacientes&#58; 41 con AR y EPID y 41 controles AR sin EPID&#46; Los pacientes con EPID presentaron un mayor porcentaje de pacientes con FR y ACPA positivos y una mayor frecuencia de serositis y osteoporosis&#46; No hubo diferencias significativas en DAS28 en casos y controles&#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;145&#41;&#44; pero los pacientes de AR con EPID presentaron peor HAQ &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;006&#41;&#46; Todos los pacientes estaban en tratamiento con FAME&#46; El an&#225;lisis multivariante mostr&#243; que los pacientes con AR exfumadores y con artritis erosiva triplicaron el riesgo de presentar EPID &#40;R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;36&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los resultados de nuestro estudio apoyan la mayor frecuencia de NIU y NINE en pacientes con AR&#44; as&#237; como la alteraci&#243;n de DLCO como el par&#225;metro m&#225;s importante&#46; Los pacientes con AR y EPID se asociaron con una enfermedad m&#225;s grave &#40;erosiones y ACPA&#41; y con el tabaco&#46;</p></span>"
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      "en" => array:3 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objectives</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To study the differences between rheumatoid arthritis &#40;RA&#41;-interstitial lung disease &#40;ILD&#41; patients and RA patients without ILD in severity markers and disease activity and to identify factors associated with the presence of ILD in RA patients&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Patients&#58; RA-ILD patients selected from a multicentre cohort in Andalusia&#44; Spain&#46; Controls&#58; RA-patients without ILD paired by sex&#44; age and disease duration&#46; Protocol&#58; RA patients are reviewed every 3-6<span class="elsevierStyleHsp" style=""></span>months in rheumatology consultation&#46; All patients are reviewed according to a predetermined protocol with systematic data collection&#46; Outcomes&#58; description of ILD type&#44; differences in severity markers and disease activity in both groups&#46; Other variables&#58; ILD type by imaging technique &#40;HRCT&#41;&#58; nonspecific interstitial pneumonia &#40;NSIP&#41;&#47;usual interstitial pneumonia &#40;UIP&#41;&#46; Lung function by PTF&#46; Activity and severity markers of arthritis by DAS28-ESR&#44; HAQ&#44; RF&#44; ACPA and erosions&#46; Treatment with DMARD&#46; Statistical analysis&#58; descriptive and paired T-test or Chi-square test followed by binary logistic regression &#40;DV&#58; ILD in patients with RA&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Eighty-two patients were included&#44; 41 RA-ILD and 41 RA controls&#46; RF and ACPA positivity&#44; serositis and osteoporosis were more frequent in RA-ILD patients&#46; No significant differences in DAS28 were observed &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;145&#41; between RA-ILD and RA control patients&#46; RA-ILD patients presented worse HAQ scores &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;006&#41;&#46; All patients were treated with disease modifying antirheumatic drugs &#40;DMARDs&#41;&#46; The risk of developing ILD in RA patients is tripled by a history of smoking or the presence of erosive arthritis &#40;R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;36&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The results of our study support the higher frequency of UIP and NSIP in RA patients&#46; DLCO is the most sensitive parameter to detect ILD in RA patients&#46; Our study showed that ILD in RA patients was associated with RA severity &#40;presence of erosions and ACPA&#41; and with a history of smoking&#46;</p></span>"
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        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AR con EPID &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AR &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Caracter&#237;sticas epidemiol&#243;gicas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Edad en a&#241;os&#44; media &#40;&#177; DE&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;9 &#40;7&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;6 &#40;8&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;898&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo&#44; mujer&#59; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;48&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;46&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;825&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo&#44; var&#243;n&#59; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;51&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;53&#44;7&#41;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Caracter&#237;sticas cl&#237;nico-anal&#237;ticas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tabaco actual</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;105&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No fumadores&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;80&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;92&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Fumadores&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;19&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Historia de tabaco</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Nunca fum&#243;&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;26&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;53&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Alguna vez fum&#243;&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;73&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;46&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tiempo de evoluci&#243;n AR&#44; meses&#44; mediana &#40;p75-p25&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116&#44;4 &#40;75&#44;5-193&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102&#44;1 &#40;71&#44;1-132&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;230&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Retraso diagn&#243;stico&#44; meses&#44; mediana &#40;p75-p25&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;1 &#40;7&#44;6-15&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;1 &#40;4&#44;9-13&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FR&#43; &#40;&#62; 10&#41;&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;95&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;82&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;077&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FR elevado &#40;&#62; 60&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;70&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;48&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;043&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ACPA&#43; &#40;&#62; 20&#41;&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;85&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;63&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t">34 &#40;82&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0 &#40;0&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;151&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6 &#40;14&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0 &#40;0&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sulfasalazina&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;14&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Metotrexato &#43; Hidroxicloroquina&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Metotrexato &#43; Sulfasalazina&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">FAME biol&#243;gico&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;36&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;36&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rituximab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">6 &#40;14&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abatacept&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;4&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Etanercept&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3 &#40;7&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;9&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infliximab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;7&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adalimumab&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;2&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t">36 &#40;87&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>DLCO&#44; media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">62&#44;1 &#40;10&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Vol&#250;menes pulmonares</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CVF &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">80&#37;&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27 &#40;65&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>CVF&#44; media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FEV1 &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">80&#37;&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20 &#40;48&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>FEV1&#44; media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FEV1&#47;CVF &#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">70&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;10&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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